ISSN:
1573-904X
Keywords:
ranitidine
;
absorption
;
secondary peak
;
bile
;
CCK
;
GI transit time
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. Ranitidine plasma concentration vs. time profiles and the extent of ranitidine absorption were examined in the presence and absence of pancreatico-biliary secretions in order to elucidate factors which may contribute to secondary peaks after oral ranitidine administration. Methods. Ranitidine solution (300 mg) was administered to 4 fasting healthy subjects via an indwelling small-bore oroenteric tube located ∼16 cm distal to the pylorus. On 3 consecutive days, subjects randomly received ranitidine alone (control), ranitidine 10 min after 0.04 μg/kg IV cholecystokinin (CCK) sufficient to cause gall bladder emptying into the duodenum, and ranitidine 30 min after inflation of an occlusive duodenal balloon located ∼10 cm distal to the pylorus to prevent pancreatico-biliary secretions from reaching the dosing port or beyond. Small bowel transit time (SBTT; min) was measured by breath H2. Serial blood samples, obtained over 12 hours in each treatment, were analyzed by HPLC to determine ranitidine AUC0−2(ng*h/mL), as well as Cmax(ng/mL) and Tmax(min) of the first and subsequent peaks, if subsequent peaks were observed. Results. Ranitidine AUC0−2and Cmax1, were not altered significantly by treatments; treatment effects on SBTT varied. Secondary peaks were observed in subjects #1 and #3 during the control treatment and subjects #2 and #4 during the CCK treatment. No secondary peaks were observed in any subject during the balloon treatment, and Tmax1was delayed. Conclusions. Results support the hypothesis that pancreatico-biliary secretions (present in the intestinal lumen during control or CCK treatment) and gastrointestinal transit time may influence the occurrence of secondary peaks in ranitidine concentration vs. time profiles.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1011908412058
